The major research objective of this proposal is to delineate the genetic, environmental and phenotypic characteristics of major gene susceptibility of a wide variety of teratogens (e.g., triamcinolone, vitamin A, diphenylhydantoin, sodium salicylate) resulting in congenital craniofacial malformations. Since the major gene under study is assumed to be either at the major histocompatibility complex (H-2) per se, or at some closely linked locus, congenic resistant pairs of mice will be used. Plotting phenotype (fetal weight, crown-rump length, individual organ malformations, tissue dysplasia, relative rates of DNA, RNA and protein synthesis, etc.) as a function of environment and developmental chronology for different maternal-fetal haplotype combinations (i.e., "reaction norms") will provide: (1) an assessment of the relative influence of the maternal and fetal haplotypes with respect to susceptibility; (2) an ordering of superiority for various haplotype combinations; and (3) determine the effect or lack of effect for maternal cytoplasmic factors. We plan to determine whether relative susceptibility and/or resistance to teratogen-induced congenital craniofacial malformations is associated with the K-end or D-end of the H-2 complex. Finally, comparing the phenotypic response to teratogen administration of C57BL/10Sn (H-2b) - B10. A/SgSn (H-2a) congenic pair with A/WySn (H-2a) - A.BY/Sn (H-2b) congenic pair, we will determine whether the same haplotypes are associated with comparatively the same or disparate effects regardless of background genome.